ArticleScientific reports2018
Intermittent C1-Inhibitor Deficiency Associated with Recessive Inheritance: Functional and Structural Insight.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Characterization of missense variants in the signal peptide of C1 esterase inhibitor.The Journal of allergy and clinical immunology · 2026Article
- Boolean Networks with Classic and New Updating Modes Applied to Genetic Regulation in Some Familial Diseases.International journal of molecular sciences · 2025Article
- Status quo and future developments in the diagnosis and treatment of hereditary angioedema.Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG · 2025Review
- Patterns of C1-Inhibitor Plasma Levels and Kinin-Kallikrein System Activation in Relation to COVID-19 Severity.Life (Basel, Switzerland) · 2024Article
- RecessiveJournal of clinical medicine · 2023Article
- Genetic Variants Leading to Urticaria and Angioedema and Associated Biomarkers.The journal of allergy and clinical immunology. In practice · 2023Article
- Insights into the pathogenesis of hereditary angioedema using genetic sequencing and recombinant protein expression analyses.The Journal of allergy and clinical immunology · 2023Article
- High Throughput Genetic Characterisation of Caucasian Patients Affected by Multi-Drug Resistant Rheumatoid or Psoriatic Arthritis.Journal of personalized medicine · 2022Article
- Review
- A novel murine in vivo model for acute hereditary angioedema attacks.Scientific reports · 2021Article
- Leveraging Genetics for Hereditary Angioedema: A Road Map to Precision Medicine.Clinical reviews in allergy & immunology · 2021Review
- The Genetics of Hereditary Angioedema: A Review.Journal of clinical medicine · 2021Review
- C1 Esterase Inhibition: Targeting Multiple Systems in COVID-19.Journal of clinical immunology · 2021Review
- Rediscovery of a forgotten disease: Hereditary Angioedema.Balkan medical journal · 2021Article
- Deriving Immune Modulating Drugs from Viruses-A New Class of Biologics.Journal of clinical medicine · 2020Review
- Genetic variants ofCentral-European journal of immunology · 2020Article
- Characterisation of a type II functionally-deficient variant of alpha-1-antitrypsin discovered in the general population.PloS one · 2019Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
C1-inhibitor is a serine protease inhibitor (serpin) controlling complement and contact system activation. Gene mutations result in reduced C1-inhibitor functional plasma level causing hereditary angioedema, a life-threatening disorder. Despite a stable defect, the clinical expression of hereditary angioedema is unpredictable, and the molecular mechanism underlying this variability remains undisclosed. Here we report functional and structural studies on the Arg378Cys C1-inhibitor mutant found in a patient presenting reduced C1-inhibitor levels, episodically undergoing normalization. Expression studies resulted in a drop in mutant C1-innhibitor secretion compared to wild-type. Notwithstanding, the purified proteins had similar features. Thermal denaturation experiments showed a comparable denaturation profile, but the mutant thermal stability decays when tested in conditions reproducing intracellular crowding.Our findings suggest that once correctly folded, the Arg378Cys C1-inhibitor is secreted as an active, although quite unstable, monomer. However, it could bear a folding defect, occasionally promoting protein oligomerization and interfering with the secretion process, thus accounting for its plasma level variability. This defect is exacerbated by the nature of the mutation since the acquired cysteine leads to the formation of non-functional homodimers through inter-molecular disulphide bonding. All the proposed phenomena could be modulated by specific environmental conditions, rendering this mutant exceptionally vulnerable to mild stress.
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